麻豆传媒

In May, we reported on positive phase III trial data on dupilumab (Dupixent) for uncontrolled chronic obstructive pulmonary disease, a condition with no approved biologic therapy. In this report, we follow up on what has happened since the results were released.

While biologic agents for asthma have been approved for 2 decades, none are currently approved for chronic obstructive pulmonary disease (COPD) -- but dupilumab (Dupixent) is expected to be the first.

At the American Thoracic Society (ATS) annual meeting in May, findings from the phase III BOREAS trial revealed that adding the interleukin (IL)-4/IL-13-targeted agent to an existing triple-therapy regimen was associated with significant improvements for COPD patients with type 2 inflammation, reducing exacerbations by approximately 30% compared with placebo over the course of a year.

Dupilumab also improved key outcomes such as quality of life, lung function, and symptoms in study participants, which comprised current or former smokers with moderate-to-severe COPD and no history of asthma.

Based on the randomized trial, the biologic was granted breakthrough therapy designation by the FDA as an additional maintenance treatment for the approximately 300,000 Americans with an eosinophilic phenotype of COPD and a history of frequent exacerbations.

Last month, drugmakers Regeneron Pharmaceuticals and Sanofi that NOTUS, a second phase III trial for dupilumab in COPD, also met its primary endpoint with overwhelming efficacy in an interim analysis.

In NOTUS, dupilumab reduced exacerbations by 34% at 52 weeks in patients with moderate-to-severe COPD and evidence of type 2 inflammation who were already on max­i­mal standard-of-care in­haled therapy. Lung function was significantly improved as early as the first 12 weeks and the effect was maintained out to 52 weeks.

Regeneron and Sanofi said that by year's end they would submit a supplemental biologics license application to the FDA -- based on data from the 1,874 COPD patients in both phase III trials put together.

Quality of life in severe COPD can be really poor, Amy Attaway, MD, of the Cleveland Clinic, told 麻豆传媒.

"I really feel for my patients," she said. "Anything to reduce exacerbations, especially in this cohort where they were targeting the most severe [COPD] I think is really, really exciting."

Attaway highlighted that another benefit of dupilumab is it's a known commodity for physicians treating COPD.

First approved in 2017 for atopic dermatitis, dupilumab is already on the market as a biologic treatment for a range of other conditions, including eosinophilic esophagitis (EoE), , and , where it was approved in 2018.

"We already have several years of data on asthma patients, [have] seen it implemented in a real-world scenario, and we see that it's been shown to be relatively safe with few side effects in most asthma patients," said Attaway.

"COPD patients are a little bit different, obviously, and that's something we need to be aware of, but we have more information at the moment than if this medication were completely new and coming down the market," she added.

E. Neil Schachter, MD, of Mount Sinai in New York City, explained to 麻豆传媒 that any relief is welcome for COPD patients. "COPD is a terrible disease that's progressive and disabling, so any new therapy in one manner or another is very desirable. We have medications that improve symptoms, but frequently they don't reduce exacerbations or the progression of the disease."

Schachter noted that, as a biologic, dupilumab stands out in its injectable administration, as opposed to an inhaled or oral therapy.

"Initially, when we started with these types of medications, patients had to come to the office to receive them on a regular basis," he said. "Now that we feel a little bit more comfortable with them, it's possible that they can do the injections ... at home after a suitable training period in a clinic or in the office."

Evidence of type 2 inflammation is present in anywhere from 20% to 40% of COPD patients, and this marker is associated with a greater risk of exacerbations.

At the ATS meeting, BOREAS presenter Surya Bhatt, MD, MSPH, of the University of Alabama at Birmingham, said that new insights into the pathophysiology and pathobiology of COPD helped move the needle after previous attempts with biologic agents for COPD yielded mixed results. Targeting type 2 inflammation "seems to be making a difference in terms of reducing exacerbation frequency and improving lung function in these patients," he said at the time.

Dupilumab remains under investigation for other diseases driven by type 2 inflammation or other allergic processes, namely pediatric EoE, chronic spontaneous urticaria, chronic pruritus of unknown origin, and COPD with evidence of type 2 inflammation and bullous pemphigoid.

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